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2.
Eur Arch Otorhinolaryngol ; 280(8): 3731-3736, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36920556

RESUMO

BACKGROUND: Dexpanthenol-containing ointments/fluids are recommended to restore impaired nasal mucosa. To date, there are no data about the influence of dexpanthenol or formulations including dexpanthenol on ciliary beat frequency (CBF) of nasal epithelial cells. METHODS: We tested the ciliary beat frequency of human nasal epithelial cells in RPMI 1640 cell solution using in vitro high-frequency video microscopy every 60 s over a period of 15 min (min). Bepanthen® solution and dexpanthenol in two clinically relevant concentrations (1.67% and 3.33%) were added to the cells. Addition of sterile water served as control group. To get a better overview, the measurements after 1 min, 5 min and 15 min were combined. RESULTS: The CBF in the control group (n = 17) after 15 min was 7.3 ± 2.6 Hz. In comparison, the CBF after 15 min was 1.8 ± 1.0 Hz in the 3.33% Bepanthen® group (n = 17) and 3.2 ± 1.2 Hz in the 1.67% group, which was statistically significantly lower in both groups (p < 0.001). With regard to the dexpanthenol group (n = 17) a CBF of 6.0 ± 2.6 Hz with 3.33% and 6.1 ± 2.4 Hz with 1.67% dexpanthenol, was detected, which was again statistically significantly lower (p = 0.06) compared to the control group except CBF at 15 min with 1.57% (n = 17; p = 0.04). In general, the effect on CBF was less pronounced with dexpanthenol compared with Bepanthen® with a statistically significant difference between the two formulations. The results were verified by calculating an analysis of variance (ANOVA). CONCLUSIONS: Bepanthen® as an ointment, solution or inhalation is commonly used in ENT for mucosal care. Our results have shown that both substances reduce CBF in clinically relevant concentrations, although the effect was more pronounced with Bepanthen® compared to dexpanthenol solution, which could be related to additives or change of physical properties in the solution. Further research is needed to assess potential clinical relevance.


Assuntos
Mucosa Nasal , Ácido Pantotênico , Humanos , Ácido Pantotênico/farmacologia , Administração por Inalação , Cílios
3.
Arch Gynecol Obstet ; 307(4): 1155-1162, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36127525

RESUMO

INTRODUCTION: The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. RESULTS: 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (ß = - 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5). DISCUSSION: Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Humanos , Feminino , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Estudos Prospectivos , Tumores do Estroma Gonadal e dos Cordões Sexuais/epidemiologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Dor , Ansiedade/epidemiologia , Ansiedade/etiologia , Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/terapia
4.
Morphologie ; 107(356): 22-27, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35277339

RESUMO

BACKGROUND: The canine fossa, a depression on the surface of the maxillary bone, is important clinically due to the nexus of the neurovascular elements which occur in this region and supply the superficial and deep structures of the face. While it is known that there is much variation in the neurovascular structures of this region, little is known about sex differences. The aim of this study was to investigate and map the neurovascular branching within the region of the canine fossa of a South African population, with particular reference to any sex differences. METHODS: Sixty hemifaces (n=30 female; n=30 male) of individuals between the ages of 40 and 100years were dissected. The origin, number of branches, connections between branches, origin of connecting branches and the distribution of the neurovascular structures associated with the mid-facial and canine fossa regions were documented. The data obtained was qualitative and was statistically analysed with SPSS v26 statistical analysis software. Frequency and contingency tables, along with Chi-squared analysis and Fischer's Exact test, were used for quantitative data analysis. RESULTS: While high levels of variation in the neurovascular elements were documented, there was no statistically significant variation between the sexes. A sex variation was only observed for the terminal branches of CN VII with females displaying a lower number of buccal nerve terminal branches than males. CONCLUSION: While only one sex difference of significance was found in the highly variable neurovascular structures resident in the region of the canine fossa, the variability of the neurovascular elements is of importance to surgeons.


Assuntos
Maxila , Caracteres Sexuais , Masculino , Feminino , Humanos , África do Sul , Cadáver
5.
Gerontol Geriatr Educ ; 44(3): 354-363, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-35377832

RESUMO

As federal partners, the Veterans Health Administration (VA) and the Indian Health Service (IHS) agreed to share resources, such as education. The VA Geriatric Scholars Program, a workforce development program, provides one of its training programs on team-based primary care of elders to clinicians working in IHS and Tribal Health Programs. The practical impact of that training is described. A mixed methods approach was applied to the course's evaluation survey at five clinics in the Northwestern Plains, Southwest, Pacific Coast, and Alaska. Quantitative approaches assessed participants' self-reported intention to improve recognition and assessment of common geriatric syndromes. A qualitative approach applied to open-ended text responses revealed intensions to improve team-based care. Among the 51 respondents in our sample, we found significant improvements in self-reported ability to recognize previously unfamiliar potential risks to elders' health and safety, t(49) = 8.0233, p < .001, as well as increased comfort with conducting geriatric assessments and increased confidence in interprofessional team-based communication. Improvements to team-based care included enhanced clinical skills, organizational factors and the need to train additional employees. This evaluation demonstrates the value of sharing resources among federal partners and its value for participants in IHS and Tribal Health Programs.


Assuntos
Geriatria , United States Indian Health Service , Estados Unidos , Humanos , Idoso , Geriatria/educação , Competência Clínica , Inquéritos e Questionários , Atenção Primária à Saúde/métodos
6.
Gerontol Geriatr Educ ; 44(3): 329-338, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-35491904

RESUMO

There is a growing need for psychologists with specialized training in geriatric mental health competencies. The Geriatric Scholars Program for Psychologists (GSP-P) was created to address this shortage within a large integrated healthcare system. In 2019, GSP-P piloted an advanced workshop designed to enhance expertise in geriatric mental health competencies among graduates of its foundational competencies core course. The workshop included 3.5 days of expert-led seminars regarding the biopsychosocial needs of older adults with chronic medical illness and was followed by completion of an individualized learning plan. This paper describes the evaluation of the course using a mixed methods with data collected prior to the workshop, immediately post-workshop, and six months post-workshop. Results indicated enthusiasm for the workshop, significant improvements in four geropsychology domains on the Pikes Peak Geropsychology Knowledge and Skill Assessment Tool, and benefit from completion of the independent learning plans. Our findings demonstrate that continued enhancement of geropsychology competencies through advanced coursework is feasible and improves knowledge and skill, particularly when combined with individualized learning plans.


Assuntos
Geriatria , Humanos , Idoso , Geriatria/educação , Psiquiatria Geriátrica/educação
7.
Appl Clin Inform ; 13(4): 961-970, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36223868

RESUMO

BACKGROUND: Involving clinician end users in the development process of clinical dashboards is important to ensure that user needs are adequately met prior to releasing the dashboard for use. The challenge with following this approach is that clinician end users can undergo periodic turnover, meaning, the clinicians that played a role in the initial development process may not be the same individuals that use the dashboard in future. OBJECTIVES: Here, we summarize our Plan, Do, Study, Act (PDSA)-guided clinical dashboard development process for the VA Geriatric Scholars Program (GSP) and the value of continuous, iterative development. We summarize dashboard adaptations that resulted from two PDSA cycles of improvement for the potentially inappropriate medication dashboard (PIMD), one of many Geriatric Scholars clinical dashboards. We also present the evaluative performance of the PIMD. METHODS: Evaluation of the PIMD was performed using the system usability scale (SUS) and through review of user interaction logs. Routine end users that were Geriatric Scholars and had evidence of 5 or more dashboard views were invited to complete an electronic form that contained the 10-item SUS. RESULTS: The proportion of Geriatric Scholars that utilized the PIMD increased for each iterative dashboard version that was produced as a byproduct from feedback (31.0% in 2017 to 60.2% in 2019). The overall usability of the PIMD among routine users was found to be above average (SUS score: 75.2 [95% CI 70.5-79.8]) in comparison to the recommended standard of acceptability (SUS score: 68) CONCLUSION: The solicitation of feedback during dashboard orientations led to iterative adaptations of the PIMD that broadened its intended use. The presented PDSA-guided process to clinical dashboard development for the VA GSP can serve as a valuable framework for development teams seeking to produce well-adopted and usable health information technology (IT) innovations.


Assuntos
Melhoria de Qualidade , Relatório de Pesquisa , Idoso , Retroalimentação , Humanos
8.
BMC Pregnancy Childbirth ; 22(1): 647, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978302

RESUMO

BACKGROUND: An acute abdomen is an emergency that requires accurate diagnosis and prompt treatment. In pregnancy, the process is even more challenging and sometimes the radiological findings are unclear. Moreover, endometriosis- related complications are rare, especially in previously unknown endometriosis. CASE PRESENTATION: We report on a case of acute endometriosis-related sigmoid perforation during pregnancy (34 weeks of gestation) due to a previously unknown deep intestinal infiltrating endometriosis with focal ulceration of the affected colonic mucosa. CONCLUSIONS: Despite the low relative risk, clinicians should be aware of possible endometriosis-associated complications in pregnancy with potentially life-threatening events, even in previously unknown endometriosis. Further studies should evaluate intestinal complications during pregnancy in relation to previous treatment of intestinal endometriosis (conservative vs. surgical).


Assuntos
Endometriose , Perfuração Intestinal , Colo Sigmoide/diagnóstico por imagem , Colo Sigmoide/cirurgia , Endometriose/complicações , Endometriose/diagnóstico , Endometriose/cirurgia , Feminino , Humanos , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Gravidez
9.
Sci Rep ; 12(1): 12310, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35853977

RESUMO

Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case-control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1-3 days before diagnosis of severe NEC (Bell's stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids-isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1-3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Aminas , Estudos de Casos e Controles , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/metabolismo , Etanolaminas , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Isoleucina , Lisina
10.
Res Gerontol Nurs ; 15(4): 193-202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35609258

RESUMO

Despite poor sleep among older adults, little is known about the sleep habits of older immigrants living in the United States. The current pragmatic qualitative descriptive study explored sleep among older Korean immigrants, using a focus group with six participants and individual phone interviews with 22 Korean immigrants aged ≥60 years. Transcripts were coded to identify underlying themes. Several thematic categories were identified under six domains: daytime function, getting ready for bed, falling asleep, awakenings during sleep, going back to sleep, and seeking advice from peers. Unhealthy sleep behaviors were found during daytime and bedtime, particularly among those who were retired/unemployed or living alone. Seeking advice from peers was common but none of the advice helped participants sleep. Sleep education programs in Korean-speaking communities can be used to target those who are socially isolated and may benefit older Korean immigrants with sleep difficulties. [Research in Gerontological Nursing, 15(4), 193-202.].


Assuntos
Emigrantes e Imigrantes , Transtornos do Sono-Vigília , Idoso , Grupos Focais , Humanos , Pesquisa Qualitativa , República da Coreia , Estados Unidos
11.
Ned Tijdschr Tandheelkd ; 129(4): 169-173, 2022 Apr.
Artigo em Holandês | MEDLINE | ID: mdl-35420274

RESUMO

While abroad, a healthy 36-year-old woman slammed head-on into a rock wall at high speed, resulting in significant facial trauma. The initial trauma care and first aid took place abroad. In the Netherlands, the woman was referred to the Department of Oral and Maxillofacial Surgery (OMFS) for reconstruction of her face and alveolar processes, gingiva and dentition. In view of the seriousness of the injuries, a 3D treatment plan was drawn up in a multidisciplinary collaboration with an OMF surgeon, an implantologist, dentist and dental technician. By making a digital setup of both the top and bottom front in advance, it was possible to work predictably. The first step consisted of bone augmentation by means of an iliac crest graft to reconstruct the major bone defects of the superior and inferior alveolar processes. Implants were then placed in the upper and lower jaws in the ideal position for the suprastructure by means of drill jigs. Within 10 months after the trauma, the implant bridges could be placed on individual zirconia frameworks to optimally restore oral function and aesthetics, completing the reconstruction.


Assuntos
Implantes Dentários , Adulto , Processo Alveolar , Transplante Ósseo/métodos , Implantação Dentária Endóssea/métodos , Feminino , Gengiva/cirurgia , Humanos , Mandíbula/cirurgia
12.
Eur Heart J Open ; 2(6): oeac069, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36600882

RESUMO

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

13.
J Immigr Minor Health ; 24(2): 403-411, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33751360

RESUMO

Poor sleep is common among older adults, affecting a wide range of health outcomes. However, little is known about sleep issues among older Korean immigrants, the fastest growing Asian American subgroup in the United States. We aimed to explore multiple factors associated with sleep among this group. We analyzed cross-sectional survey data from 43 older immigrants living in two large Korean communities in Southern California. Perceived sleep quality was significantly associated with gender, living arrangement, employment status, mental health, and sleep-related beliefs (all p-values < 0.05). Living with someone and being employed for wages were significantly uniquely associated with better sleep quality, accounting for demographic and health-related factors (R2 = 51.8%, adjusted R2 = 38.7%, p = 0.002). These findings suggest a potential role of sociocultural factors on sleep. Further studies are needed to confirm these findings and to inform a sleep intervention program tailored to the characteristics of older Korean immigrants.


Assuntos
Emigrantes e Imigrantes , Qualidade do Sono , Idoso , Asiático/psicologia , Estudos Transversais , Demografia , Humanos , República da Coreia/epidemiologia , Autorrelato , Estados Unidos/epidemiologia
14.
S Afr Med J ; 111(4): 315-320, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33944763

RESUMO

BACKGROUND: Workplace bullying and other negative workplace behaviours are problems that need to be addressed across many work settings, including at universities. OBJECTIVES: To examine the prevalence of bullying among academics, and factors associated with bullying, in a faculty of health sciences (FHS) of a South African university. METHODS: All academic staff, except senior managers, were invited to participate by completing a self-administered, web-based questionnaire hosted on REDCap. In adition to sociodemographic information, the survey collected information on bullying, and the factors associated with experiences of workplace bullying. Survey data were exported to Stata 13 for analysis. The data were weighted to take account of the distribution of staff in the FHS. Chi-square tests and a multiple logistic regression model for bullying were utilised. RESULTS: The majority of study participants were white (52%), female (70%) and South African (85%). Bullying in the workplace was experienced by 58% of respondents, of whom 44% experienced bullying more than once, and 64% of participants had witnessed bullying. Being female (adjusted odds ratio (aOR) 1.83; 95% confidence interval (CI) 1.14 - 2.93; p<0.05) and being jointly appointed as both a clinician in a health facility and an academic in the university (aOR 1.73; 95% CI 1.29 - 2.32; p<0.001) increased the odds of experiencing workplace bullying. CONCLUSIONS: A combination of strategies is needed, including clear FHS policies to prevent bullying, training in bullying prevention and critical diversity, and positive practice environments.


Assuntos
Centros Médicos Acadêmicos , Bullying , Docentes de Medicina/psicologia , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Bullying/estatística & dados numéricos , Docentes de Medicina/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , África do Sul/epidemiologia , Inquéritos e Questionários , Adulto Jovem
15.
J Am Geriatr Soc ; 69(3): 798-805, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33453084

RESUMO

Older adults are more likely to seek mental health care through integrated care settings such as primary care. Currently, there exists a significant shortage of mental health providers trained in geropsychology and integrated care competencies. To address this need within the Veterans Health Administration, a national workforce development program was extended to include psychologists, which is called the Geriatric Scholars Program-Psychology Track (GSP-P). The GSP-P has two overarching educational program aims: (1) to improve geropsychology competencies of practicing VA psychologists, particularly those working within integrated settings (e.g., primary care) and (2) enrich psychologists' abilities to enact change in their clinical settings. Ninety-eight VA clinicians participated in the GSP-P, which includes a multi-day in-person course, from 2014 to 2018. Participants completed measures assessing confidence and self-reported knowledge in geropsychology and integrated care competencies pre-course and 3-months post-completion. Two-weeks post-course participants responded to open-ended survey questions regarding their perceptions of the course and potential applications of learning. Significant improvements in confidence in and knowledge of geropsychology and integrated care competencies emerged from pre-course to 3-months post-completion. Qualitative findings demonstrated that participants valued the face-to-face, integrated multimodal educational program. Findings provided insights regarding clinicians' planned application of the knowledge acquired, such as modifying treatments for older patients. Specialized workforce programs such as the GSP-P have a significant, positive impact on the care of older Veterans.


Assuntos
Competência Clínica , Geriatria/educação , Psicologia/educação , Idoso , Currículo , Prestação Integrada de Cuidados de Saúde/organização & administração , Feminino , Geriatria/normas , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Psicologia/normas , Pesquisa Qualitativa , Estados Unidos , United States Department of Veterans Affairs , Veteranos/psicologia
16.
J Mol Med (Berl) ; 99(1): 147-158, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278000

RESUMO

HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. KEY MESSAGES: • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.


Assuntos
Infecções por HIV/imunologia , Antígenos HLA-B/imunologia , Células Matadoras Naturais/imunologia , Monócitos/imunologia , Linfócitos T/imunologia , Receptores Toll-Like/agonistas , Adulto , Idoso , Idoso de 80 Anos ou mais , Citocinas/imunologia , Feminino , Humanos , Imunidade Inata , Inflamação/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Lipopeptídeos/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Oligodesoxirribonucleotídeos/farmacologia , Linfócitos T/efeitos dos fármacos , Receptor Toll-Like 9/agonistas , Adulto Jovem
17.
Biomed Opt Express ; 11(11): 6389-6412, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33282497

RESUMO

Two main bottlenecks prevent time-domain diffuse optics instruments to reach their maximum performances, namely the limited light harvesting capability of the detection chain and the bounded data throughput of the timing electronics. In this work, for the first time to our knowledge, we overcome both those limitations using a probe-hosted large area silicon photomultiplier detector coupled to high-throughput timing electronics. The system performances were assessed based on international protocols for diffuse optical imagers showing better figures with respect to a state-of-the-art device. As a first step towards applications, proof-of-principle in-vivo brain activation measurements demonstrated superior signal-to-noise ratio as compared to current technologies.

18.
HNO ; 68(12): 916-921, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-33128107

RESUMO

BACKGROUND: CD8+ cells are key players in the identification and elimination of cancer cells. Cancers can escape an effective T cell response by inducing an exhausted cell state, which limits the cytotoxic capacity of the effector cells. Among other mechanisms, new checkpoint inhibitors reactivate exhausted, dysfunctional T cells. CD8+ T cells can eliminate tumor cells after presentation of tumor-specific antigens via antigen-presenting cells (APCs). APC-mediated tumor recognition is mainly stimulated by Toll-like receptors (TLRs). OBJECTIVE: This study investigates the effect of TLR agonists on APCs as well as stimulatory and inhibitory signaling pathways of the T cell-APC interaction. MATERIALS AND METHODS: Gene expression of interleukin (IL)12 and programmed death ligand 1 (PD-L1) was analyzed by quantitative polymerase chain reaction (qPCR) after 0, 8, 24, and 48 h of CD14+ cell stimulation with CpG. Protein expression of inhibitor of nuclear factor kappa B (IκBα) after CpG stimulation was investigated by western blot. CD8+ T cells were stimulated for 72 h with or without programmed cell death protein 1 (PD-1) checkpoint blockade and analyzed for expression of PD­1, Tim­3, CTLA4, and Lag3 by flow cytometry. RESULTS: TLR stimulation (by unmethylated CpG DNA) of APCs upregulates immunostimulatory signals such as IL12 expression but also activates immunoinhibitory signaling pathways such as PD-L1 expression. This signaling is NF-κB dependent. After blockade of the PD-1/PD-L1 signaling pathway, overexpression of other immune checkpoint inhibitory receptors was observed-a potential explanation for lacking therapeutic responses after TLR stimulation with PD­1 checkpoint blockade. CONCLUSION: TLR stimulation causes APCs in the tumor microenvironment to upregulate PD-L1 in an NF-κB-mediated fashion, thereby contributing to CD8+ T cell exhaustion. The effect of PD­1 blockade after TLR stimulation might be impaired due to upregulation of other checkpoint inhibitors.


Assuntos
Células Apresentadoras de Antígenos , Linfócitos T CD8-Positivos , Transdução de Sinais , Receptores Toll-Like , Antígeno B7-H1/metabolismo , NF-kappa B/fisiologia , Receptores Toll-Like/antagonistas & inibidores , Microambiente Tumoral
19.
Mol Med ; 26(1): 82, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883198

RESUMO

BACKGROUND: Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. METHODS: We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. RESULTS: Four days of IA LPS exposure causes a decreased PGP9.5- and S100ß-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. CONCLUSIONS: The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Corioamnionite/veterinária , Sistema Nervoso Entérico/patologia , Doenças dos Ovinos/etiologia , Animais , Biomarcadores , Modelos Animais de Doenças , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/etiologia , Feminino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Gravidez , Nascimento Prematuro , Ovinos
20.
BMC Pediatr ; 20(1): 421, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883280

RESUMO

BACKGROUND: In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. METHODS: Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 - December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 - May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. RESULTS: All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. CONCLUSION: The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.


Assuntos
Síndrome do Desconforto Respiratório do Recém-Nascido , Tensoativos , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Estudos Retrospectivos , Resultado do Tratamento
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